HTLV-1 infection of donor-derived T cells might promote acute graft-versus-host disease following liver transplantation

Abstract

Acute graft versus host disease (aGVHD) is a rare, but severe complication of liver transplantation (LT). It is caused by the activation of donor immune cells in the graft against the host shortly after transplantation, but the contributing pathogenic factors remain unclear. Here we show that human T cell lymphotropic virus type I (HTLV-1) infection of donor T cells is highly associated with aGVHD following LT. The presence of HTLV-1 in peripheral blood and tissue samples from a discovery cohort of 7 aGVHD patients and 17 control patients is assessed with hybridization probes (TargetSeq), mass cytometry (CyTOF), and multiplex immunohistology (IMC). All 7 of our aGVHD patients display detectable HTLV-1 Tax signals by IMC. We identify donor-derived cells based on a Y chromosome-specific genetic marker, EIF1AY. Thus, we confirm the presence of CD4+Tax+EIF1AY+ T cells and Tax+CD68+EIF1AY+ antigen-presenting cells, indicating HTLV-1 infection of donor immune cells. In an independent cohort of 400 patients, we verify that HTLV-1 prevalence correlates with aGVHD incidence, while none of the control viruses shows significant associations. Our findings thus provide new insights into the aetio-pathology of liver-transplantation-associated aGVHD and raise the possibility of preventing aGVHD prior to transplantation.

Donor-derived infections in solid organ transplant recipients

“…Acute graft versus host disease (aGVHD) is a rare, but severe complication of liver transplantation and maybe caused by the activation of donor immune cells in the graft against the host shortly after transplantation. Of interest that a recent study showed that HTLV-1/2 infection of donor-derived T cells might promote aGVHD [ 31 ▪▪ ] in liver transplant recipients.…”

One-way donor-to-recipient human leukocyte antigen mismatch and graft-versus-host disease in liver transplantation: an observational study of a single-center experience in Korea

“…HCC was also numerically more frequent in the HLA-OWMM group, but without statistical significance (64.5% vs. 41.4%, P=0.379). The pretransplant MELD score was significantly lower in the HLA-OW-MM group than in the control group(11 [IQR,(8)(9)(10)(11)(12)(13)(14)(15) vs. 15 [IQR, 10-25]; P=0.013]. In the HLA-OWMM group, 14.3% of donors were deceased, compared to 32.9% in the control group (P=0.057).…”

“…GVHD develops in donor lymphocytes that are transplanted along with the liver graft [ 6 , 7 ]. Consequently, infection of donor T cells with human T cell lymphotropic virus type-1 has emerged as a significant risk factor [ 8 ]. While CD2-blockers and TNF-α antagonists have been suggested as potential treatment options, no confirmed treatment for GVHD currently exists [ 9 - 11 ].…”